MT3 shows apparently different properties and function from MT1 even though they have 70% sequence homology. Possibly the two inserts, Thr5 and a negatively charged hexapeptide at position-55 in MT3, play important roles. A series of MT3 variants around the EAAEAE hexapeptide have been prepared by site-directed mutagenesis and their properties and reactivity towards pH, EDTA and DTNB have been studied. Our detailed studies revealed that the EAAEAE insert is essential to the property of MT3. It is the hexapeptide insert, to some extent, making the MT3 alpha-domain looser and lower stability of the metal-thiolate cluster, which could be accessed more easily.

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http://dx.doi.org/10.1093/protein/gzg127DOI Listing

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Article Synopsis
  • hGIF is a protein that inhibits neuron growth, with unique structural features, including two specific insertions compared to metallothionein.
  • The acidic hexapeptide EAAEAE(55-60) insertion is crucial for hGIF's inhibitory function, as shown by the decreased activity of a mutant lacking this segment.
  • Research involving molecular dynamics simulations revealed that this insert influences the protein's structure and interactions, enhancing its biological activity by affecting solvent accessibility and metal release.
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The effect of the EAAEAE insert on the property of human metallothionein-3.

Protein Eng

December 2003

Chemical Biology Laboratory, Department of Chemistry, Fudan University, Shanghai 200433.

MT3 shows apparently different properties and function from MT1 even though they have 70% sequence homology. Possibly the two inserts, Thr5 and a negatively charged hexapeptide at position-55 in MT3, play important roles. A series of MT3 variants around the EAAEAE hexapeptide have been prepared by site-directed mutagenesis and their properties and reactivity towards pH, EDTA and DTNB have been studied.

View Article and Find Full Text PDF

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